Phenylacetic Acid → Mandelic Acid

Temperature

60 °C

Phenyl acetic acid (1.82 Kg, 8.89 mol, 1.1 eq) and nitrile (1.62 Kg, 8.08 mol, 1.0 eq) were dissolved in DMSO (8 L) at 25° C. To this solution was added K2CO3 (2.46 Kg, 17.8 mol, 2.2 eq) in portions to control off gassing. The purple slurry was heated to 60° C. and aged overnight. Upon reaction completion the reaction mixture was inversely quenched in to a mixture of (16 L) of MTBE, (12.9 L) DI water and (3.5 L) methane sulfonic acid slowly. After mixing for 30 minutes the aqueous layer was removed and the organic layer was washed with 16 L of DI water and concentrated to dryness. MeOH (4 L) was added and the solution concentrated to dryness twice, until the residual MTBE was <5% by GC. To the product, MeOH (22 L) and 8.3 mL of methane sulfonic acid were charged, and the batch was heated to 63° C. over 15 hours, until 99% conversion. The reaction was cooled by ramping to 20° C. and the resulting suspension was filtered and washed with MeOH (2×3 L). The solid cake was dried under N2 to provide 74% yield with 101.8 wt % potency and 99.5 A % purity. Chloroisomer content was 2.16 A %. A second recrystallization using 23.6 L of MeOH and heating to 68° C. obtained the desired product in 67% with 100 wt % potency, 99.7 A % purity and 0.74 A % chloroisomer content. Recrystallization process was repeated until <0.5 A % of chloroisomer content was achieved.

1. customUpon reaction completion the reaction mixture
2. customwas inversely quenched in to a mixture of (16 L) of MTBE, (12.9 L) DI water and (3.5 L) methane sulfonic acid slowly
3. additionAfter mixing for 30 minutes the aqueous layer
4. customwas removed
5. washthe organic layer was washed with 16 L of DI water
6. concentrationconcentrated to dryness
7. additionMeOH (4 L) was added
8. concentrationthe solution concentrated to dryness twice
9. additionTo the product, MeOH (22 L) and 8.3 mL of methane sulfonic acid were charged
10. temperaturethe batch was heated to 63° C. over 15 hours, until 99% conversion
11. temperatureThe reaction was cooled
12. customby ramping to 20° C.
13. filtrationthe resulting suspension was filtered
14. washwashed with MeOH (2×3 L)
15. customThe solid cake was dried under N2
16. customto provide 74% yield with 101.8 wt % potency and 99.5 A % purity
17. customA second recrystallization
18. temperatureheating to 68° C.

ORD record

ord-00b1d068fb424292b643261b52a3c904

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08183293B2